Jatrophatrione synthesis

Ir Catalyst, ester aldol condensation, enantioselective 6 Jatrophatrione synthesis 24... 

Leo Paquette of Ohio State recently reported (J. Am. Chem. Soc. 125 1567, 2003) the total synthesis of jatrophatrione 1 and citlalitrione 2. These diterpenes, which share a central highly-subsituted 5-9-5 core, show remarkable tumor-inhibitory activity. 

TOTAL SYNTHESIS OF JATROPHATRIONE, AN UNPRECEDENTED [5.9.5] TRICYCLIC ANTILEUKEMIC DITERPENE... 

L.A. Paquette and co-workers accomplished the first total synthesis of the antileukemic agent jatrophatrione. " This natural product has a [5.9.5] fused tricyclic skeleton with a trans-BIC ring fusion. The key step in their approach was the Grab fragmentation to obtain the tricyclo[5.9.5] skeleton. The tetracyclic 1,3-diol was monomesylated on the less hindered hydroxyl group and then treated with potassium fert-butoxide, triggering the concerted fragmentation to afford the desired tricyclic product in almost quantitative yield. 

Furthermore, intramolecular hydrosilylation has been used as a key step in the total synthesis of complex natural products, such as jatrophatrione 141,... 

A transannular ene-reaction was featured in the reaction cascade that was used by Paquette and co-workers in their synthesis of the [5.9.5] tricyclic diterpenes jatrophatrione and citlalitrione. This reaction cascade involved initiating the stereoselective anionic oxy-Cope reaction of 43 by treatment with KOf-Bu and 18-crown-6 followed by trapping the enolate 44 with methyl iodide to give intermediate 45 (Scheme 20.13). This was followed by the spontaneous transannular ene-reaction to give 46 in 70% overall yield. It was converted to jatrophatrione and citMitrione after additional transformations. 

SCHEME 20.13. The transannular ene-reaction in the synthesis of jatrophatrione and citlalitrione. 

Paquette LA, Yang J, Long YO. Concerning the antileukemic agent jatrophatrione the first total synthesis of a [5.9.5] tricyclic diterpene. J. Am. Chem. Soc. 2002 124 6542-6543. 

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